Post-transplant Year Research Articles

The Impact of Reduced Immunosuppression on Alloimmunity: A Retrospective Study of Pediatric Kidney Transplant Recipients.

Kidney transplantation is the best treatment for end-stage kidney disease but requires immunosuppressive medications, which have significant side effects. Many pediatric recipients experience these side effects, leading to dosage reductions, which potentially increase the risk of alloimmunity. We aimed to describe the alteration in immunosuppressive medication, explore the reasons for the reductions, and assess the potential impact on alloimmunity. Data from 49 pediatric kidney transplant recipients receiving an allograft from 2009 to 2020 were retrospectively studied. The recipients were screened for HLA antibodies after the transplantation. The median age of recipients was 11 years (IQR 8), with a median follow-up of 5 years (IQR 5). Eighty percent of the transplantations were corticosteroid-free. During follow-up, 11% developed de novo donor-specific antibodies (dnDSA), and 60% had detectable HLA antibodies. The 1-year rejection rate was 4%. Immunosuppressive medication was altered substantially in most recipients, resulting in 72% being on mono- or dual therapy with a reduced mycophenolate mofetil (MMF) dosage by the end of the first posttransplant year. The median MMF dose was nearly half of the intended. Tacrolimus levels were maintained close to the target of 5 ng/mL. No association was found between reduced immunosuppression and dnDSA or rejections. Reductions were primarily due to MMF-related side effects: leukopenia in 77%, gastrointestinal issues in 34%, and infections with Epstein-Barr virus, cytomegalovirus, and BK polyomavirus in 49%. Reduced MMF with a sufficient trough tacrolimus level in a population of mainly corticosteroid-free pediatric kidney transplant recipients did not lead to unacceptable alloimmunity.

Hip geometry and strength remain stable the first year after kidney transplantation – an ibandronate/placebo post hoc analysis

Abstract The sensitivity of bone mineral density (BMD) to identify patients with high fracture risk after kidney transplantation is low, wherefore alternative tools are needed. Hip Structure Analysis (HSA) provides an estimation of hip structural geometry and strength based on conventional DXA scans for hip analyses. We aimed to investigate the effect of antiresorptive therapy on hip geometrical and strength parameters by HSA. In a post hoc analysis of a 12-month randomized, double-blind, placebo-controlled trial evaluating the effect of ibandronate in addition to active vitamin D and calcium in kidney transplant recipients (KTR), we re-analyzed dual total hip and femoral neck DXA scans to measure cortical bone thickness (CBT) in the femoral neck (CBTNECK), calcar (CBTCALCAR), and shaft (CBTSHAFT), along with femur neck width, hip axis length, and to estimate Buckling Ratio and Strength Index. DXA measurements were performed within 5 weeks after transplantation and repeated at 10 weeks and 1-year post-transplant. The study included a total of 127 de novo KTR with eGFR >30 mL/min at baseline. The five geometrical and the strength and stability hip parameters remained stable over the first post-transplant year irrespective of antiresorptive therapy. We detected no statistically significant between-group differences in any of the HSA measures. Change in geometrical hip parameters and Buckling Ratio over the study duration was not correlated with change in plasma parathyroid hormone or change in dual total hip BMD. In this study, the so far largest of HSA in KTR, antiresorptive therapy with ibandronate for 12 months did not affect measures of hip geometry or strength. Clinical Trial Registration: www.clinicaltrials.gov as NCT00423384, EudraCT number 2006-003884-30.

Impact of Pelvic Calcification Severity on Renal Transplant Outcomes: A Prospective Single-Center Study.

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0-4), PCS Group 2 (PCS 5-19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management.

Identification and Validation of a Threshold for Early Posttransplant Bronchoalveolar Fluid Hyaluronan that Distinguishes Lung Recipients at Risk for CLAD

BackgroundFew tools exist for early identification of patients at risk for chronic lung allograft dysfunction (CLAD). We previously showed hyaluronan (HA), a matrix molecule that regulates lung inflammation and fibrosis, accumulates in bronchoalveolar lavage fluid (BALF) and blood in CLAD. We aimed to determine if early posttransplant HA elevations inform CLAD risk. MethodsHA was quantified in 3080 BALF and 1323 blood samples collected over the first posttransplant year in 743 adult lung recipients at 5 centers. The relationship between BALF or blood HA and CLAD was assessed using Cox models with a time-dependent binary covariate for “elevated” HA. Potential thresholds for elevated HA were examined using a grid search between the 50th and 85th percentile. The optimal threshold was identified using fit statistics, and the association between the selected threshold and CLAD was internally validated through iterative resampling. A multivariable Cox model using the selected threshold was performed to evaluate the association of elevated HA with CLAD considering other factors that may influence CLAD risk. ResultsBALF HA levels >19.1ng/mL (65th percentile), had the largest hazard ratio for CLAD (HR 1.70, 95% CI 1.25–1.31; p<0.001), optimized fit statistics, and demonstrated robust reproducibility. In a multivariable model, the occurrence of BALF HA >19.1 ng/mL in the first posttransplant year conferred a 66% increase in the hazards for CLAD (adjusted HR 1.66, 95% CI 1.19–2.32; p=0.003). Blood HA was not significantly associated with CLAD. ConclusionsWe identified and validated a precise threshold for BALF HA in the first posttransplant year that distinguishes patients at increased CLAD risk.

Hospital-free days in the first year after lung transplantation and subsequent survival

RationaleComplications occurring during the first post-operative year after lung transplantation increase the risk of long-term mortality. These events often lead to prolonged and repeated hospitalizations. ObjectivesWe sought to assess the relationship between days outside the hospital or hospital-free days (HFD) during the first post-transplant year among 1-yr survivors and subsequent retransplant-free survival. MethodsIn a single-center study, we derived total inpatient days (initial transplant episode, readmission, and emergency room/observation) from the electronic medical record of lung transplant recipients who survived one year. The cohort was divided into HFD quartiles and Kaplan-Meir curves of subsequent transplant-free survival were compared with log-rank analysis. A Cox proportional hazards model was used to test the association of HFD with outcome and adjusted for selected variables. ResultsAmong 238 patients, 42 deaths and 2 retransplants occurred after a median of 3.6 yr post-transplant. The median HFD was 341 (IQR:324, 348). Estimated transplant-free survival at 3 and 5 yrs post-transplant in the lowest quartile of HFD (79% and 56%, respectively) was considerably worse compared with the first quartile (98% and 94%; P < 0.01). Fewer hospital-free days were associated with subsequent death or retransplant [HR: 0.90 (95% CI: 0.85, 0.94; P < 0.001) for each 10-day increase] and remained significant after adjusting for several potentially confounding variables. ConclusionsHFD during the first year after lung transplantation is a predictor of subsequent long-term outcome and may be a useful surrogate marker for clinical trials during the early post-operative period.

Rejection Surveillance After Heart Transplantation: Is Paired Noninvasive Testing the New Gold Standard?

Rejection surveillance after heart transplantation has traditionally relied on numerous endomyocardial biopsies, most of which occur during the first posttransplant year. With the introduction of gene expression profiling and, more recently, donor-derived cell-free DNA, a great proportion of surveillance is being performed noninvasively with both tests. Although patients have welcomed the use of paired testing because of the decreased risk and inconvenience, interpretation of both tests can sometimes be challenging, particularly when the test results are discordant. Growing evidence from both single-center experiences and large national databases has given insights that have allowed the field to operationalize dual testing and provide physicians with algorithms to approach paired testing. The increased use of noninvasive testing has also begun to challenge the role of biopsy as the gold standard for graft monitoring, not only for rejection but over the life of the heart transplant. In a growing number of circumstances, cell-free DNA not only may be a better means of assessing rejection but could also redefine how clinicians approach the diagnosis and even treatment of graft injury. As the heart transplant community garners more experience and generates more data, the current paradigms of heart transplant surveillance will continue to be challenged.

Unraveling complexity: morbidity factors in elderly kidney transplant recipients.

The rising prevalence of end-stage renal failure in the elderly has led to an increased number of kidney transplantations in older individuals. While age does not solely determine transplant eligibility, frailty in elderly recipients significantly impacts post-transplant outcomes, particularly within the first year. The RETRAITE (REnal TRAnsplantIon ouTcome in Elderly recipients) study, a single-center retrospective cohort study at Grenoble Alpes University Hospital (France), examined kidney transplant recipients aged 70years and above transplanted between 2015 and 2020. The composite primary endpoint was defined as either of any hospital stay exceeding 40days, death and/or return to dialysis within the first post-transplant year. The study explored risk factors for recipient and graft survival, rejection, hospitalizations over 40days, and severe infections during the initial post-transplant year. Over six years, 149 patients aged 70years or older received transplants. Eleven patients died, and seven returned to dialysis within the first year, corresponding to a 1-year graft survival rate of 87.9%. At 1year, 49 patients (33%) met the composite endpoint. There was a significant association between the composite endpoint and curative anticoagulation [odds ratio (OR) 5.20; P<.001], peripheral arteriopathy (OR 3.14; P<.001) and delayed graft function (OR8.24; P<.001). This cohort then was merged with a cohort of 150 younger kidney transplanted patients and we confirmed these results. Time on dialysis, prolonged cold ischemia and donor age contributed to higher morbidity and mortality. Conversely, preemptive and living donor transplants were associated with lower morbidity and mortality. In this cohort aged over 70years, age alone did not statistically correlate with increased morbidity and mortality. Variables related to grafts and donors, especially curative anticoagulation, were linked to poorer outcomes, emphasizing the favorable impact of preemptive and living donor transplants on morbidity and mortality in elderly patients.

Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study.

The current study aimed to determine the optimal tacrolimus trough levels for balancing graft survival and patient safety following kidney transplantation. We conducted a retrospective cohort study involving 11,868 kidney transplant recipients from five medical centers. The association between tacrolimus exposures (periodic mean trough level, coefficient of variability, time in therapeutic range) and composite allograft outcome (de novo donor specific antibody, biopsy-proven rejection, kidney dysfunction, and graft failure), as well as safety outcomes (severe infection, cardiovascular events, malignancy, and mortality) were assessed. Data were sourced from Clinical Data Warehouses and analyzed using advanced statistical methods, including Cox marginal structural models with inverse probability treatment weighting. Tacrolimus levels of 5.0-7.9ng/mL and 5.0-6.9ng/mL during the 2-12 month and 12-72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes. During the first post-transplant year, the adjusted hazard ratios (aHR) for composite allograft outcomes were: 0.69 (95% CI 0.55-0.85, P<0.001) for 5.0-5.9ng/mL; 0.81 (95% CI 0.67-0.98, P=0.033) for 6.0-6.9ng/mL; and 0.73 (95% CI 0.60-0.89, P=0.002) for 7.0-7.9ng/mL (compared to levels ≥8.0ng/mL). For the 6-year composite outcomes, aHRs were 0.68 (95% CI 0.53-0.87, P=0.002) for 5.0-5.9ng/mL and 0.65 (95% CI 0.50-0.85, P=0.001) for 6.0-6.9ng/mL. These optimal ranges showed reduced rates of severe infection (6y), malignancy (6y), and mortality (1y). This multicenter study provides robust evidence for optimal tacrolimus trough levels during the periods 2-12 and 12-72 months following kidney transplantation.

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

Late nephrectomy in infants with congenital nephrotic syndrome of the Finnish type.

Bilateral nephrectomy is commonly performed in patients with congenital nephrotic syndrome of the Finnish type. The optimal timing of nephrectomy is unclear. Growth, thromboembolic events, infections, transplant-related complications and ability to eat were compared between infants with early (Group 1, n = 13) and late (Group 2, n = 10) nephrectomy. 'Early' was defined as nephrectomy at 7-kg body weight followed by peritoneal dialysis and 'late' as nephrectomy at ≥10 kg followed by 3-4 weeks of haemodialysis and kidney transplantation. Patients were followed until the end of the first post-transplant year. Dialysis time was significantly longer in group 1 than in group 2. Late nephrectomy did not increase the risk for thromboembolic events or septicaemia but decreased tube feeding dependency (group 1 69% vs. group 2 20%, p = 0.019). Motor development at transplantation was considered normal in 80% of the infants with late nephrectomy compared to 31% in the early nephrectomy group (p = 0.019); however, the difference between the groups disappeared by the end of the follow-up. Infants with late nephrectomy have comparative outcome but less feeding tube dependency and better motor development during the first post-transplant months compared to infants with early nephrectomy.

#1713 Blood pressure goals in kidney transplant recipients: an analysis of the collaborative transplant study

Abstract Background and Aims Hypertension is an independent risk factor for cardiovascular disease, the leading cause of death in kidney transplant recipients. Because there is no “one size fits all” approach to blood pressure targets, particularly in the heterogenous group of kidney transplant recipients, identification of subgroup-specific targets, considering factors like age and sex, may be appropriate. However, currently available studies are limited because of sample sizes, and no subgroup analyses have been performed examining the effects of different blood pressure targets on allograft and patient survival. The aim of our study was to investigate the impact of different ACC/AHA blood pressure categories on graft survival and patient mortality and to identify subgroup-specific targets. Method This large-scale retrospective study included 1-year blood pressure data from 62, 556 kidney transplant recipients reported to the Collaborative Transplant Study from 209 centers in 39 countries. Hypertension was categorized according to 2017 ACC/AHA guidelines. The primary outcomes were death-censored graft failure and patient mortality during post-transplant year 1 to 6. Multivariable Cox regression analysis was performed to control for immunologic and nonimmunologic confounders. Results One year after transplantation, 77% of kidney transplant recipients had hypertension. Hypertension stages 1 (130–139/80–89 mmHg), 2a (140–159/90–99 mmHg), and 2b (≥160/≥100 mmHg) were associated with an 8%, 34%, and 102% increased risk of death-censored graft failure, respectively, whereas elevated blood pressure levels (120–129/&amp;lt;80 mmHg) did not significantly increase the risk. Patient mortality was only significantly higher in those with hypertension stage 2b with a Hazard Ratio of 1.21 (95% CI, 1.08–1.36; P &amp;lt; .001). In addition, the impact of hypertension stages on death-censored graft failure varied in different subpopulations (Fig. 1). Female recipients, younger recipients, recipients who received kidneys from donors younger than 60 years, re-transplanted recipients, and recipients with pre-transplant HLA antibodies had a significantly increased risk of death-censored graft failure associated with higher blood pressure levels (Fig. 1). Kidney transplant recipients with hypertension stage 2 continued to have an increased risk of graft failure one year after transplantation, even when they achieved normal blood pressure in the second year. Conclusion This study highlights the importance of treating hypertension early after kidney transplantation to improve long-term graft and patient survival. Attention should be paid to female, younger, and sensitized recipients, who may particularly benefit from optimal blood pressure control.

#2132 Recipient outcomes after laparoscopic versus open living donor nephrectomy: a propensity score-matched cohort study

Abstract Background and Aims Kidney transplantation is the optimal treatment for end-stage renal disease. To meet the growing demand for kidney allografts and to ensure the well-being of donors, laparoscopic nephrectomy has been adopted leading to superior donor outcomes. However, data on recipient outcomes of laparoscopically retrieved grafts are underreported. The aim of the study is to estimate the impact of laparoscopic compared to open living donor nephrectomy (LDN, ODN) on recipient outcomes in the first-year post-transplant. Method This was an observational cohort study of primary data on 396 recipients who had undergone living kidney transplantation from January 2011 to December 2021 at the Clinic of Nephrology and Renal Transplantation of ‘Laiko’ hospital. Since October 2018 laparoscopic surgery has supplanted ODN in the reporting center. Graft function, the risk of adverse events, patient and graft survival within the first-year post-transplantation, were evaluated. A propensity score analysis was applied (2:1 nearest-neighbor matching, with a caliper width of 0.05). As a robustness check, the analysis was rerun on the sub-groups of low and high immunological risk patients. Results After propensity score matching, 389 patients were analyzed. One-year post-transplantation, renal function (−0.074 mg/dl, p: 0.063) patient (99.44% vs 100%, p: 0.27) and graft (99.43% vs 100%, p: 0.13) survival were statistically equal among LDN and ODN recipients. Laparoscopically retrieved grafts demonstrated statistically higher risk of delayed graft function (10.1%, p: 0.032) and higher risk for transfusion (12.9%, p:0.022). The risk for acute rejection, surgical complications and infections (Fig. 1), as well as the length of hospital stay did not differ between the two groups. Kidney function at one year was similar in LDN and ODN patients, regardless of the immunological risk. Low immunological risk patients demonstrated comparable risk of adverse events in the first post-transplant year. High-immunological risk patients after LDN after LDN exhibited greater risk for reoperation (16%, p: 0.0078) urologic complications (19.6%, p: 0.042) and bacterial infections (7.1%, p: 0.027) compared to ODN recipients during the first year after transplantation. Conclusion The results indicate that one-year post-transplantation, renal function, patient and graft survival are equivalent among recipients of allografts procured either laparoscopically or by open surgery, with similar risk of adverse events.

Tacrolimus-loaded Drug Delivery Systems in Vascularized Composite Allotransplantation: Lessons and Opportunities for Local Immunosuppression.

Long-term systemic immunosuppression is needed for vascularized composite allotransplantation (VCA). The high rate of acute rejection episodes in the first posttransplant year, the development of chronic rejection, and the adverse effects that come along with this treatment, currently prevent a wider clinical application of VCA. Opportunistic infections and metabolic disturbances are among the most observed side effects in VCA recipients. To overcome these challenges, local immunosuppression using biomaterial-based drug delivery systems (DDS) have been developed. The aim of these systems is to provide high local concentrations of immunosuppressive drugs while reducing their systemic load. This review provides a summary of recently investigated local DDS with different mechanisms of action such as on-demand, ultrasound-sensitive, or continuous drug delivery. In preclinical models, ranging from rodent to porcine and nonhuman primate models, this approach has been shown to reduce systemic tacrolimus (TAC) load and adverse effects, while prolonging graft survival. Localized immunosuppression using biomaterial-based DDS represents an encouraging approach to enhance graft survival and reduce toxic side effects of immunosuppressive drugs in VCA patients. Preclinical models using TAC-releasing DDS have demonstrated high local immunosuppressive effects with a low systemic burden. However, to reduce acute rejection events in translational animal models or in the clinical reality, the use of additional low-dose systemic TAC treatment may be envisaged. Patients may benefit through efficient graft immunosuppression and survival with negligible systemic adverse effects, resulting in better compliance and quality of life.

The reduced function allele SLCO1B1 c.521T>C is of no practical relevance for the renal graft function over the first post-transplant year in patients treated with mycophenolic acid.

It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression. In a 12-month observational cohort study, consecutive adult patients were repeatedly assessed for eGFR. The SLCO1B1 c.521C>T variant allele carriers (exposed) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and eGFR trajectory was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation. The adjusted eGFR slopes from day 1 to day 28 (daily), and from day 28 to day 365 (monthly) were practically identical in exposed (n = 86) and control (n = 168) patients [geometric means ratios (GMR) = 0.99, 95% confidence interval (CI) = 0.92-1.06 and GMR = 0.98, 0.94-1.01, respectively]. The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in exposed and controls [rate ratios (RR) = 0.94, 0.49-1.84 and RR = 1.08, 0.74-1.58, respectively]. The pharmacokinetic analysis did not signal meaningful differences regarding exposure to MPA, overall (exposed n = 23, control n = 45), if cotreated with cyclosporine (n = 17 vs. n = 26) or with tacrolimus (n = 8 vs. n = 17). In patients treated with MPA, variant allele SLCO1B1 c.521T>C appears of no practical relevance regarding the 12-month renal graft function, MPA safety and exposure to MPA at early steady-state.

Preoperative Risk Assessment of Early Kidney Graft Loss.

A large proportion of potential organ donors are not utilized for kidney transplantation out of risk of early allograft loss because of donor-related characteristics. These can be summarized using kidney donor profile index (KDPI). Because KDPI affects the choice of the recipient, the predictive ability of KDPI is tied to recipient attributes. These have been questioned to explain most of the predictive ability of KDPI. This study aims to quantify the effect of the donor on early graft loss (EGL) by accounting for nonrandom allocation. This study included patients undergoing kidney transplantation from deceased donors between 2014 and 2020 from the Scientific Registry of Transplantation Recipients. EGL, defined as a return to dialysis or retransplantation during the first posttransplant year, was the primary endpoint. Nonrandom allocation and donor-recipient matching by KDPI necessitated the use of inverse probability treatment weighting, which served to assess the effect of KDPI and mitigate selection bias in a weighted Cox regression model. The study comprised 89 290 transplantations in 88 720 individual patients. Inverse probability treatment weighting resulted in a good balance of recipient covariates across values of continuous KDPI. Weighted analysis showed KDPI to be a significant predictor for short-term outcomes. A comparable (in terms of age, time on dialysis, previous transplants, gender, diabetes status, computed panel-reactive antibodies, and HLA mismatches) average recipient, receiving a kidney from a donor with KDPI 40-60 had a 3.5% risk of EGL increased to a risk of 7.5% if received a kidney from a KDPI >95 donor (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7). However, for all-cause survival KDPI was less influential. The predictive ability of KDPI does not stem from recipient confounding alone. In this large sample-sized study, modeling methods accounting for nonindependence of recipient selection verify graft quality to effectively predict short-term transplantation outcomes.

Efficacy of surveillance bronchoscopy versus clinically indicated bronchoscopy for detection of acute lung transplant rejection: a systematic review and meta-analysis.

Acute allograft rejection after lung transplantation significantly increases the risk of developing bronchiolitis obliterans syndrome, a form of chronic lung allograft dysfunction and the leading cause of mortality beyond the initial post-transplantation year. There are two diagnostic approaches available for monitoring lung transplant recipients: clinically indicated bronchoscopy (CIB) and surveillance bronchoscopy (SB). The efficacy of both methods and their relative superiority in detecting acute rejection have not been conclusively determined. We systematically searched the MEDLINE, Embase, Cochrane and Scopus databases from inception until 10 October 2023 for prospective studies comparing the efficacy of SB and CIB. Meta-analysis using a random effects model was performed for three observational cohort studies, totalling 122 patients with 527 bronchoscopies. Overall, neither SB nor CIB had a higher likelihood of detecting acute lung transplant rejection of any grade. Subsequent subgroup analyses showed no advantage for SB in detecting minimal rejection (grade A1), but an inverse association was observed for higher-grade rejection. In conclusion, our study found no significant difference in detecting acute lung transplant rejection between SB and CIB. However, due to the limited number of studies and small sample sizes, larger prospective studies are urgently needed to definitely determine whether there truly exists no difference between SB and CIB in detecting acute rejection, particularly A1 minimal rejection.

Impact of donor-specific antibody with low mean fluorescence intensity on allograft outcomes in kidney transplant

BackgroundImmune-mediated rejection is the most common cause of allograft failure in kidney transplant (KT) patients. Exposure to alloantigen, including human leukocyte antigen (HLA), results in the production of donor-specific antibodies (DSA). There are limited data about low levels of mean fluorescence intensity (MFI) DSA, especially post-transplantation. This study evaluated allograft outcomes in KT patients with low MFI DSA. MethodsFrom January 2007 to December 2021, KT patients who were tested for post-transplant DSA at Ramathibodi Hospital, Bangkok, Thailand, with the DSA MFI ≤ 1000 were evaluated. These KT patients were categorized into two groups: very low DSA (VLL; MFI = 1–500) and low DSA (LL; MFI = 501–1000). All KT patients were evaluated for the primary outcomes, such as the incidence of acute rejection, serum creatinine levels at one and five years after transplantation as well as allograft and patient survivals. ResultsAmong 36 KT patients 25 were included as those with VLL and 11 as those with LL. The LL group had significantly higher T-cell mediated allograft rejection (TCMR) than the VLL group (45% vs. 12%, P = 0.04). In addition, 10 patients, 5 in the VLL group and 5 in the LL group developed antibody-mediated allograft rejection (ABMR). Both TCMR and ABMR were confirmed by biopsy results. There was a trend toward higher MFI in KT patients with ABMR than without ABMR (P = 0.22). At 5 post-transplant years, serum creatinine, allograft and patient survivals were comparable between these two groups. Furthermore, the univariate and multivariate analyzes revealed that the LL group was a high risk for rejection. ConclusionLow MFI DSA values after transplantation may be associated with a higher incidence of rejection, but this finding did not show differences in allograft and patient survival in this study's analysis.

Different profiles of acute graft pyelonephritis among kidney recipients from standard or elderly donors.

Acute graft pyelonephritis (AGPN) is a relatively common complication in kidney transplants (KTs); however, the effects on allograft function, diagnostic criteria, and risk factors are not well established. Retrospective analysis of all consecutive adult KTs was performed between 01 January 2011 and 31 December 2018 (follow-up ended on 31 December 2019) to examine the association between the diagnosis of AGPN (confirmed with magnetic resonance imaging [MRI]) during the first post-transplantation year and graft outcomes. Among the 939 consecutive KTs (≈50% with donors ≥60 years), we identified 130 MRI-confirmed AGPN episodes, with a documented association with recurrent and multidrug-resistant bacterial urinary tract infections (UTIs) (p < 0.005). Ureteral stenosis was the only risk factor associated with AGPN (OR 2.9 [95% CI, 1.6 to 5.2]). KTs with AGPN had a decreased allograft function at the first year (ΔeGFR 6 mL/min/1.73 m2 [-2-15] in non-AGPN vs. -0.2 [-6.5-8.5] in AGPN, p < 0.001), with similar and negative profiles in KTs from standard or elderly donors. However, only KTs with AGPN and a donor <60 years showed reduced death-censored graft survival (p = 0.015); most of this subgroup received anti-thymocyte globulin (ATG) induction (40.4% vs. 17.7%), and their MRI presented either a multifocal AGPN pattern (73.9% vs. 56.7%) or abscedation (28.3% vs. 11.7%). No difference was noted in death-censored graft survival between early (<3 months post-KT) or late (3-12 months) AGPN, solitary/recurrent forms, or types of multidrug-resistant pathogens. Linear regression confirmed the independent role of multifocal pattern, abscedation, ATG induction, and donor age on the eGFR at the first year. AGPN, influenced by multifocal presentation, ATG induction, donor age, and abscedation, affects kidney function and significantly impacts allograft survival in KTs with donors <60 years.

Liver transplantation program at the Burnasyan Federal Biophysical Center: experience in 500 procedures

To analyze the features and outcomes of 500 liver transplantations in adults over a 12-year period. The study included data on 500 liver transplantations between May 2010 and April 2023. We analyzed 483 adults who underwent transplantation and 438 candidates for this procedure. All data were obtained from local liver transplantation registry. Clinical outcomes were recorded as of June 1, 2023. Statistical analysis was performed using the Statistica 12 (StatSoft Inc., USA) and Jamovi version 2.3.21.0 software (Jamovi project). Among 438 patients in the waiting list between January 2012 and May 2023, liver transplantation was performed in 198 (45%) cases including 27 (6%) transplantations from living-related donors and 37 (8%) procedures in other centers. There were 109 (25%) deaths. The 1- and 3-year survival rates were 81% (95% CI 76-85%) and 50% (95% CI 42-59%), respectively. Organs from deceased donors (n=134, 27%) and living-related donors (n=366, 73%) were used for transplantations. Redo transplantations were necessary in 21 (4%) cases. The median age of recipients was 45 years (range 18-72), median MELD-Na score - 16 (range 6-43). The most common indications for transplantation were viral cirrhosis (37%), cholestatic liver disease (16%), and hepatocellular carcinoma (14%). Monotherapy with calcineurin inhibitors was performed in 39% of cases, combination of calcineurin inhibitors and glucocorticoids, antimetabolites or mTOR inhibitors - 52%, three-component schemes - 8% of cases. Annual, 5- and 7-year survival rates of recipients after primary transplantation were 87% (95% CI: 84-90%), 79% (95% CI: 75-83%) and 75% (95% CI: 70-80%), respectively. In case of liver transplantation from living-related donors, these values were 89% (95% CI: 86-92%), 84% (95% CI: 80-88%) and 80% (95% CI: 75-85%), after transplantation from deceased donors - 81% (95% CI: 74-88%), 66% (95% CI: 57-76%) and 58% (95% CI: 45-72%), respectively. Liver transplantation is highly effective for patients with diffuse and focal liver diseases. Living donors not only significantly improve availability of this technology, but also provide substantial advantages in outcomes compared to liver transplantation from deceased donors, reducing the likelihood of recipient mortality by 10% after one post-transplantation year and by more than 20% after five years.

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients.

Bone loss after kidney transplantation is highly variable. We investigated whether changes in bone turnover markers associate with bone loss during the first post-transplant year. Bone mineral density (BMD) was measured at 0 and 12 months, with biointact parathyroid hormone, bone-specific alkaline phosphatase (BALP), intact procollagen type I N -terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured at 0, 3, and 12 months post-transplant ( N =209). Paired transiliac bone biopsies were available in a subset ( n =49). Between-group differences were evaluated by Student's t test, Wilcoxon signed-rank test, or Pearson's chi-squared test. Changes in BMD varied from -22% to +17%/yr. Compared with patients with no change (±2.5%/yr), patients who gained BMD had higher levels of parathyroid hormone (236 versus 136 pg/ml), BALP (31.7 versus 18.8 μ g/L), and Intact PINP (121.9 versus 70.4 μ g/L) at time of transplantation; a greater decrease in BALP (-40% versus -21%) and Intact PINP (-43% versus -13%) by 3 months; and lower levels of Intact PINP (36.3 versus 60.0 μ g/L) at 12 months post-transplant. Patients who lost BMD had a less marked decrease, or even increase, in Intact PINP (+22% versus -13%) and TRAP5b (-27% versus -43%) at 3 months and higher Intact PINP (83.7 versus 60.0 μ g/L) and TRAP5b (3.89 versus 3.16 U/L) at 12 months compared with patients with no change. If none of the biomarkers decreased by the least significant change at 3 months, an almost two-fold (69% versus 36%) higher occurrence of bone loss was seen at 12 months post-transplant. Bone loss after kidney transplantation was highly variable. Resolution of high bone turnover, as reflected by decreasing bone turnover markers, associated with BMD gain, while increasing bone turnover markers associated with bone loss.